New Clinical Trial: Ofatumumab and Bortezomib in Untreated Waldenstrom Macroglobulinemia

A Multicenter Phase II Study of Ofatumumab and Bortezomib (OB) in Previously Untreated Patients with Waldenström Macroglobulinemia

Update: this study is closed to enrollment. 
The Weill Cornell Lymphoma Program is now enrolling patients in a new clinical trial for people with Waldenstrom Macroglobulinemia who have not been treated. The study sponsor is the National Comprehensive Cancer Network (NCCN). The principal investigator at Weill Cornell is Dr. Peter Martin.

For more information about the study, please call Amelyn Rodriguez, RN at (212) 746-1362 or email Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older
  • Diagnosis of Waldenstrom Macroglobulinemia (WM)
  • No prior anti-neoplastic therapy for WM
  • Detailed eligibility reviewed when you contact the study team

Study Details

Although there is currently no standard treatment for first-line management of WM, most clinicians and investigators believe that anti-CD20 directed therapy should compromise part of the regimen. Because it was the first therapeutic monoclonal antibody approved by the FDA , rituximab has been evaluated more than any antibody and has shown modest effects with limited toxicity. However, new treatments for WM are needed.

Ofatumumab has been approved for treatment of relapsed/refractory Chronic Lymphocytic Leukemia (CLL). It is an anti-CD20 monoclonal antibody that compared favorably to rituximab in a recent Phase 2 trial in patients with WM.

The purpose of the study is to determine how well previously untreated people with Waldenstrom Macroglobulinemia respond to treatment with ofatumumab in combination with bortezomib (Velcade). The study will also evaluate the safety of ofatumumab in combination with bortezomib.

Treatment Plan

Study participants will have four 28-day cycles of induction phase therapy. Participants will receive treatments weekly for three weeks, and then have a rest period (no treatment) for the fourth week. After the four cycles, there will be 4 weeks of no therapy and then 4 cycles of maintenance phase therapy. The maintenance cycles will be 28 days long. Participants will receive three weeks of treatment, then a resting period (no treatment) for the fourth week. This will be followed by four weeks of rest (no treatments). Then a new cycle will begin. Thus a new cycle of maintenance treatment will begin every 8 weeks. The entire period for both induction and maintenance therapy will be 1 year (52 weeks).

Participants will be followed until disease progression or 5 years from study entry, whichever comes first.

Update from ASH 2011: New treatments for mantle cell lymphoma are on the horizon

By Peter Martin, MD

Update: this study is closed to enrollment. 

Arguably the most exciting news to come from the American Society of Hematology (ASH) meeting this year was the presentation by Dr. Michael Wang of preliminary results from the phase 2 trial of PCI-32765 for patients with previously treated mantle cell lymphoma (MCL). PCI-32765 is an oral (pill form) inhibitor of an enzyme called Bruton’s Tyrosine Kinase (BTK). BTK plays an important role in communicating pro-survival signals from the cell microenvironment to the nucleus of the cell. Inhibition of BTK by PCI-32765 demonstrated promise in patients with MCL in a national phase 1 that was open at Weill Cornell Medical College. This phase 2 study, also open at Weill Cornell, demonstrated a response rate of approximately 60-70% with little toxicity (mostly mild gastrointestinal side-effects). It is too early to determine how long these effects will last or whether there are any side effects that will become apparent with longer treatment. Click here for more information about this trial.

Dr. Beata Holkova presented the results of a National Cancer Institute (NCI) phase 2 study that was open at several institutions across the country, including Weill Cornell. The trial evaluated the combination of bortezomib (FDA-approved for treatment of patients with previously treated MCL) plus the histone deacetylase inhibitor vorinostat. The combination demonstrated synergistic activity in preclinical studies and showed promised in earlier trials in patients with multiple myeloma. Preliminary results from this NCI trial were encouraging, particularly in the group of patients with MCL that had never been treated with bortezomib. The trial is ongoing. Click here for more information about this study.